Formation of a dihydropyridine derivative as a potential cross-link derived from malondialdehyde in physiological systems.
Malondialdehyde is a major oxidation product of lipids which is capable of cross-linking the collagen of the cardiovascular system. Identification of cross-links usually involves degradative procedures. In this paper, we use a novel, direct, approach using nuclear magnetic resonance to identify early and labile products. Initial model studies show that malondialdehyde reacts with lysine to form a dihydropyridine derivative rather than the unstable imidopropene Schiff base previously reported. The aldehydes on the pyridine ring could react further to cross-link collagen and stiffen the aorta, thereby promoting further glycation, a process that would be accelerated in diabetes.
Slatter
D A
DA
Collagen Research Group, Division of Molecular and Cellular Biology, University of Bristol, Langford, UK. D.A.Slatter@bris.ac.uk
Murray
M
M
Bailey
A J
AJ
D003432:Cross-Linking Reagents; D004095:Dihydropyridines / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism*; D011437:Propylamines / Q000378:metabolism
D003432:Cross-Linking Reagents; D004095:Dihydropyridines; D011437:Propylamines; C002315:N(alpha)-acetyllysine; D008315:Malondialdehyde; C038806:1,4-dihydropyridine; D008239:Lysine